Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100,Israel
Molecular recognition between biological macromolecules and surfaces plays a crucial role in the understanding of various biological systems. Antibodies with their almost infinitely variable region are the most astounding and flexible tool that nature has evolved to cope with recognition in the widest possible range. For the purpose of studying the rules of molecular recognition, it would appear convenient to elucidate series of antibody-antigen structures where the antigen surface is controlled and well known. The surfaces of crystals composed of small organic molecules well answer the requirements of systematic variability, control, and knowledge of the structure at the molecular level. We have proposed that crystal surfaces may behave as antigens that when introduced into organisms, are capable of inducing specific antibodies. An antibody developed against a crystal could bear in its binding site a structured imprint of a number of molecules exposed on the crystal surface.
A number of monoclonal antibodies that interact specifically with the crystals of cholesterol monohydrate and 1,4 dinitrobenzene crystals were individually separated and produced. Three types of antibodies were investigated: antibodies that recognize the dinitrobenzene crystals but not those of cholesterol, antibodies that recognize cholesterol crystals, but not dinitrobenzene, and antibodies that recognize both crystals. In contrast to the monoclonal antibodies raised against the component molecules, none of these antibodies interacts with the corresponding molecular haptens. This unequivocally demonstrates their affinities to organized crystal surfaces rather than isolated molecules. Furthermore, some antibodies exhibit preferential recognition of some faces of a crystal relative to others.
In order to understand the molecular basis of the interaction between the antibody and the crystal surface, we identified the specifically recognized crystal surfaces, and thus the structure of the recognized regions. On the antibody side we determined the sequence of the specific antibody variable regions, and built molecular models of their binding site. For three out of four antibodies that recognize crystals specifically, the molecular interaction between the binding site of the antibody and the recognized crystal face is based both on geometrical fit and on chemical forces.
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